Causal relationship between sex hormone-binding globulin, 25-hydroxyvitamin D and polycystic ovary syndrome: a two-sample bidirectional Mendelian randomization study

Many studies have reported that sex hormone-binding globulin (SHBG) and 25-hydroxyvitamin D (25(OH)D) are important factors affecting polycystic ovary syndrome (PCOS), but their interrelationship remains controversial. Our study employed bidirectional Mendelian randomization analysis to elucidate the causal relationships between SHBG, 25(OH)D, and PCOS. The genetic loci closely related to SHBG, 25(OH) D and PCOS were extracted from large-sample GWAS data as instrumental variables. Five algorithms, namely, MR‒Egger regression, weighted median, inverse variance weighting (IVW), simple mode and weighted mode, were used for bidirectional Mendelian randomization analysis. In addition, the Cochran Q test was used to evaluate heterogeneity, the MR‒Egger intercept plot and the funnel plot were used to test horizontal pleiotropy, and sensitivity analysis was performed with the leave-one-out method to evaluate whether there was a correlation between SHBG, 25(OH)D and PCOS. We found that a decrease in SHBG and 25(OH) D levels is a genetic susceptibility factor for PCOS, whereas PCOS does not lead to a change in SHBG and 25(OH) D levels. In addition, a positive causal relationship was found between SHBG and 25(OH) D, with a decrease in SHBG leading to a corresponding decrease in 25(OH) D, whereas the change in SHBG was independent of 25(OH) D.